FDAs Pharmaceutical Quality Initiative Workshop

1
FDAs Pharmaceutical Quality Initiative Workshop

• Breakout Session B
• Product Process Development Design
• for Biologicals and Biotech Products
• March 2, 2007

2
FDAs Pharmaceutical Quality Initiative Workshop B

• 1. QbDScientific Product / Process Design Space
• Product / Process Cross Functional Teams in DEV
• Dynamic process defines the product
• As knowledge of activity based on protein
  structure increases, integrate cross functionally
  (include Quality)
• Risks Raw Materials / Intermediates down
  stream effects
• Risk Assessment CPQA CPP in Development
• Discrimination High/Low Experts Risk
  Assessment
• Product High Clinical / Experience Critical
  PQA
• Process Parameters Critical PQA High PP (DOE)
  CPP
• Critical Process Parameters 80/20 80/16/4
• Critical Product Quality Attributes - 1st
• Critical Process Parameters 2nd
• Design Space Definition Iterative CPQA / CPP

3
FDAs Pharmaceutical Quality Initiative Workshop B

• 2. Design Space
• Determination of Design Space
• Prior Scientific Knowledge / Data Mining
• Designed Experiments (small scale DOE) Critical
  Product Quality Attributes / CPPs
• Animal Models
• Clinical Performance (may be limited for CPP)
• Clinical Databases (across similar products -
  MAbs)
• Design Space knowledge can be a starting point
  for extending CPQA / CPPs across products /
  platforms
• CPPs are the foundation for validation

4
FDAs Pharmaceutical Quality Initiative Workshop B

• 3. Quality System
• Quality System is Essential Q10
• Quality Unit involved in Development
• Distinction between quality concepts and Quality
  Unit
• Quality Approval of DEV Plan Gate Reviews
• Double Handshakes Throughout Development
• Knowledge Management System
• Right Approach at the Right Time
• Lab Notebooks vs. Formal Protocols
• Development Reports
• Tiered approach to details (various levels of
  summary data)
• Sophisticated IT Systems
• Dont rely on Tribal Knowledge
• Relational Databases

5
FDAs Pharmaceutical Quality Initiative Workshop B

• 4 . Industry Communications to FDA
• Development Summary Report
• Risk Assessment Summaries
• Critical vs Non-critical rationale CPQA / CPP
• DOE Results in support of CPPs
• CPQAs in the Development Section
• CPPs in the Manufacturing Section
• Upfront Agreement FDA / Industry
• Design Space Definition
• QbD Pilot Program Requirements
• MAb Platform Design Space Master File
• Comparability Protocols-Process/Facility Changes
• PAI Inspection Expectations

6
FDAs Pharmaceutical Quality Initiative Workshop

• Breakout Session H
• Process Control Post-Approval Product Life
  Cycle
• for Biologicals and Biotech Products
• March 2, 2007

7
FDAs Pharmaceutical Quality Initiative Workshop H

• 1. QbD Application Post-approval
• Design Space is a living document
• Design Space should be periodically reviewed as
  part of the Quality System
• Risk Assessment and growing knowledge should be
  used as a tool to update the Design Space
• Donnas Humpty Dumpty approach to Design Space
• Design Space is the Egg
• Control Space is the Yolk

8
FDAs Pharmaceutical Quality Initiative Workshop H

• 2. Design Space Expansion Due to Experience
• Design Space is dynamic, a living document and
  needs to be updated based on new experience and
  may be expanded (FDA approval)
• Additional experience may find new control
  parameters
• Failures and investigation reports could be
  included in the update of Design Space
• Operations can be adjusted within the Design
  Space
• Expansion of the Design Space to accommodate
  operations outside Design Space is considered to
  be a change and needs to be reported to FDA
  appropriate experimentation / knowledge would be
  needed by firms to expand Design Space for FDA
  approval

9
FDAs Pharmaceutical Quality Initiative Workshop H

• 2. Design Space Expansion Due to Experience
  Contd
• Control Space is where, within the Design Space,
  a firm would normally operate operations outside
  the Operating Space but within the Design Space
  should be investigated but not reported to FDA as
  is currently done in validated processes
• Based on additional knowledge defining a robust
  Design Space, tests may be eliminated and
  specifications modified with FDA agreement
• It is comforting to Industry to report changes
  within the Design Space to FDA

10
FDAs Pharmaceutical Quality Initiative Workshop H

• 3. QbD Applied Across Product Class/Platform
• Super Design Space capture family or platform
• Concept Universal Platform Approach
• Potential for restricted Design Space
• Utilization of previous knowledge
• Platform
• Some data still needed
• Risk assessment specific to product
• Certain vaccines have one process with multiple
  strains running across one platform
• Case-by-case
• MOA
• Characterization
• Process
• Patient specific drugs ultimate robust Design
  Space

11
FDAs Pharmaceutical Quality Initiative Workshop H

• 4. QbD Implementation
• Comparability Protocols
• Change Design Space because of new facility or
  different scale Comparability Protocol needs to
  be updated
• Unit Operations Design Space easier step approach
• Process Capability and clinical experience
  determines Design Space
• Shrinking the Design Space because process is
  less robust is a dilemma for regulatory reporting

12
FDAs Pharmaceutical Quality Initiative Workshop H

• 4. QbD Implementation
• How do we deal with the uncertainty in Design
  Space development? Well deal with it the same
  way we dealt with it without Design Space
• Can data from monitoring and control within the
  Design Space be used to eliminate a specification
  without the requirement to submit a Comparability
  Protocol ?
• Use of deviation reports (with appropriate
  additional experimentation) to expand the Design
  Space
• Leverage 20 years of data, at set point, to
  define (a very narrow) Design Space

13
FDAs Pharmaceutical Quality Initiative Workshop H

• 5. QbD Reduction of Regulatory Supplements
  YES !
• Current Operational Regulatory Mechanisms
• Comparability Protocols
• Principles are the same for all categories but
  vastly different scope of scientific data
• Cell lines new IND ?
• Unit operations
• Process parameters
• Raw materials
• Unit Operations Design Space
• Quality Attributes Specific to Unit Op
• Plus Linkage to Downstream Unit Ops
• Some Aspects of Design Space are specific to
  equipment and facility